Secretin induces rapid increases in inositol trisphosphate, cytosolic Ca 2+ and diacylglycerol as well as cyclic AMP in rat pancreatic acini

Abstract

Previous studies have shown that the dose-response relationship for secretin-stimulated cyclic AMP accumulation is different from that for secretin-stimulated enzyme secretion in the rat exocrine pancreas. Here we show that secretin concentrations of 10 -10 M and higher stimulated a rise in cyclic AMP levels, with maximum effect on cyclic AMP accumulation being achieved already with 10 -8 M-secretin. However, at this concentration of secretin, enzyme secretion rates were approximately half-maximal. Unexpectedly, at concentrations of secretin greater than 10 -8 M there was evidence suggestive of phosphatidylinositol bisphosphate hydrolysis with rapid increase in inositol trisphosphate, cytosolic free calcium and diacylglycerol content of rat pancreatic acini. Furthermore, there was a dose-response relationship among secretin concentration (in the range 10 -8 M-2 x 10 -6 M), increases in inositol trisphosphate and increases in cytosolic free calcium ([Ca 2+](i)). Contrary to what has been previously believed, these results clearly indicate that in rat pancreatic acini secretin not only stimulates cyclic AMP accumulation but also raises inositol trisphosphate, [Ca 2+](i) and diacylglycerol. Thus, two second messenger systems may play a role in the regulation of secretin-induced amylase release.